Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation
- Conditions
- Advanced NSCLCMetastatic Lung Cancer
- Interventions
- Combination Product: PembrolizumabCombination Product: Cisplatin/Carboplatin
- Registration Number
- NCT05609578
- Lead Sponsor
- Mirati Therapeutics Inc.
- Brief Summary
Study CA239-0010 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for patients with advanced NSCLC with TPS ≥ 1%, TPS \<50% and KRAS G12C mutation
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
- All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting
- Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was >1 year prior to first dose of study treatment)
- Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting
- Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment
- Active brain metastases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort C Adagrasib oral dose of 400 mg twice daily tablets Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles Cohort E Adagrasib oral dose of 400 mg twice daily tablets Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles) Cohort E Cisplatin/Carboplatin Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles) Cohort C Cisplatin/Carboplatin Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles Cohort A: PD-L1 TPS≥ 1% (Closed) Adagrasib oral dose of 400 mg twice daily tablets Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles Cohort E Pembrolizumab Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles) Cohort C Pembrolizumab Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) for Cohort A and E 30 months Defined as the percent of patients documented to have a confirmed CR or PR
Progression-free Survival (PFS) at six months for Cohort C 30 months PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) 30 months Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.
Overall Survival (OS) 30 months Defined as time from date of first study treatment to date of death due to any cause
Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss). Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months Concentration data from this study will be pooled with other studies and exposure parameters derived using population PK methods. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed to report results from participants enrolled in the study and described in the Participant Flow module.
Adverse Events 30 months Defined as number of patients with treatment emergent AEs
Progression-free Survival (PFS) 30 months Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Cohorts C and E: DLTs during SLI (Safety Lead In) 30 months Defined as those patients in the SLI of the study who have received at least 80% of the assigned dose of adagrasib during the first cycle on study, or interrupted or discontinued study treatment during the first cycle due to a DLT.
Trial Locations
- Locations (166)
Local Institution - 017-792
🇬🇪Tbilisi, Georgia
Local Institution - 017-793
🇬🇪Tbilisi, Georgia
Local Institution - 017-452
🇧🇷Fortaleza, Brazil
Local Institution - 017-455
🇧🇷Jau, Brazil
Local Institution - 017-454
🇧🇷Rio De Janeiro, Brazil
Local Institution - 017-456
🇧🇷Sao Paolo, Brazil
Local Institution - 017-694
🇷🇸Kragujevac, Serbia
Local Institution - 017-691
🇷🇸Sremska Kamenica, Serbia
Local Institution - 017-457
🇧🇷Barretos, Brazil
Local Institution - Unk025
🇺🇸Anchorage, Alaska, United States
Local Institution - 017-591
🇺🇸Glendale, Arizona, United States
Local Institution - 017-821
🇺🇸Phoenix, Arizona, United States
Local Institution - Unk047
🇺🇸Anaheim, California, United States
Local Institution - 017-936C
🇺🇸Fountain Valley, California, United States
MemorialCare - Orange Coast Medical Center
🇺🇸Fountain Valley, California, United States
Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton
🇺🇸Fullerton, California, United States
Local Institution - Unk004
🇺🇸Loma Linda, California, United States
Local Institution - 017-961
🇺🇸Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Local Institution - 017-872-I
🇺🇸Aurora, Colorado, United States
Local Institution - 017-872-G
🇺🇸Boulder, Colorado, United States
Local Institution - 017-872-D
🇺🇸Colorado Springs, Colorado, United States
Local Institution - 017-872-J
🇺🇸Colorado Springs, Colorado, United States
Local Institution - 017-872-B
🇺🇸Denver, Colorado, United States
Local Institution - 017-872-F
🇺🇸Denver, Colorado, United States
Local Institution - 017-872-A
🇺🇸Lakewood, Colorado, United States
Local Institution - 017-872-C
🇺🇸Littleton, Colorado, United States
USOR - Rocky Mountain Cancer Centers - Lone Tree
🇺🇸Lone Tree, Colorado, United States
Local Institution - 017-872-E
🇺🇸Pueblo, Colorado, United States
Local Institution - 017-872-H
🇺🇸Thornton, Colorado, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
The Oncology Institute of Hope and Innovation - Lakeland
🇺🇸Lakeland, Florida, United States
Local Institution - Unk076
🇺🇸Miami, Florida, United States
Local Institution - Unk055
🇺🇸Orlando, Florida, United States
Local Institution - Unk062
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Local Institution - 017-820J
🇺🇸Fairway, Kansas, United States
Local Institution - 017-820A
🇺🇸Kansas City, Kansas, United States
Local Institution - 017-820B
🇺🇸Kansas City, Kansas, United States
Local Institution - 017-820C
🇺🇸Kansas City, Kansas, United States
Local Institution - 017-820H
🇺🇸Kansas City, Kansas, United States
Local Institution - 017-820I
🇺🇸Overland Park, Kansas, United States
University of Kansas Cancer Center - Westwood/Richard and Annette Bloch Cancer Care Pavilion
🇺🇸Westwood, Kansas, United States
Local Institution - 017-965
🇺🇸Lexington, Kentucky, United States
Local Institution - Unk009
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Local Institution - Unk039
🇺🇸Burlington, Massachusetts, United States
Local Institution - Unk069
🇺🇸Detroit, Michigan, United States
Local Institution - Unk018
🇺🇸Lansing, Michigan, United States
Henry Ford Medical Center - Columbus
🇺🇸Novi, Michigan, United States
Local Institution - 017-838B
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 017-838C
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Metro-Minnesota Community Oncology Research Consortium (MMCORC)
🇺🇸Saint Louis Park, Minnesota, United States
Local Institution - 017-838A
🇺🇸Saint Louis Park, Minnesota, United States
Local Institution - 017-820F
🇺🇸Kansas City, Missouri, United States
Local Institution - 017-820E
🇺🇸Kansas City, Missouri, United States
Local Institution - 017-820D
🇺🇸Lee's Summit, Missouri, United States
Local Institution - 017-820G
🇺🇸North Kansas City, Missouri, United States
Local Institution - Unk008
🇺🇸Osage Beach, Missouri, United States
Local Institution - Unk058
🇺🇸Springfield, Missouri, United States
Local Institution - 017-080
🇺🇸Babylon, New York, United States
Local Institution - 017-945
🇺🇸Bronx, New York, United States
Local Institution - 017-083
🇺🇸Bronx, New York, United States
Local Institution - 017-088
🇺🇸Brooklyn, New York, United States
Hematology-Oncology Associates of Central New York - Brittonfield - East Syracuse
🇺🇸East Syracuse, New York, United States
Local Institution - 017-087
🇺🇸New Hyde Park, New York, United States
Local Institution - 017-085
🇺🇸New York, New York, United States
Local Institution - 017-082
🇺🇸Patchogue, New York, United States
Local Institution - 017-081
🇺🇸Port Jefferson Station, New York, United States
New York Cancer & Blood Specialists - Cancer Center - Research Headquarters
🇺🇸Port Jefferson Station, New York, United States
Local Institution - 017-086
🇺🇸Port Jefferson, New York, United States
Local Institution - 017-442
🇧🇷Curitiba, Brazil
Local Institution - 017-084
🇺🇸Riverhead, New York, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
Local Institution - 017-836
🇺🇸Kettering, Ohio, United States
Local Institution - 017-916
🇺🇸Memphis, Tennessee, United States
Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Local Institution - Unk056
🇺🇸Dallas, Texas, United States
Local Institution - 017-848
🇺🇸Houston, Texas, United States
Local Institution - 017-999
🇺🇸Irving, Texas, United States
USOR - Texas Oncology Northeast Texas - Longview Cancer Center
🇺🇸Longview, Texas, United States
Local Institution - 017-878-B
🇺🇸Palestine, Texas, United States
Local Institution - 017-878-C
🇺🇸Paris, Texas, United States
Local Institution - 017-878-A
🇺🇸Tyler, Texas, United States
Local Institution - Unk010
🇺🇸Salt Lake City, Utah, United States
Local Institution - 017-814-A
🇺🇸Arlington, Virginia, United States
Local Institution - Unk066
🇺🇸Fairfax, Virginia, United States
Virginia Cancer Specialists - Fairfax Office
🇺🇸Fairfax, Virginia, United States
Local Institution - 017-814-B
🇺🇸Gainesville, Virginia, United States
Local Institution - 017-814-C
🇺🇸Reston, Virginia, United States
PeaceHealth St. Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Local Institution - Unk036
🇺🇸Huntington, West Virginia, United States
Local Institution - 017-458
🇧🇷Natal, Rio Grande Do Norte, Brazil
Local Institution - 017-446
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Local Institution - 017-453
🇧🇷Itajai, Santa Catarina, Brazil
Local Institution - 017-695
🇨🇱Vina Del Mar, Valparaiso, Chile
Local Institution - 017-697
🇨🇱Providencia, Chile
Local Institution - 017-696
🇨🇱Santiago, Chile
Local Institution - 017-698
🇨🇱Temuco, Chile
Institut de Cancerologie de lOuest - Angers
🇫🇷Angers Cedex 02, France
Centre Francois Baclesse
🇫🇷Caen Cedex 5, France
Centre Hospitalier Intercommunal de Creteil
🇫🇷Creteil, France
Centre Georges Francois Leclerc
🇫🇷Dijon cedex, France
Hopital Michallon
🇫🇷La Tronche, France
Local Institution - 017-688
🇫🇷Lille, France
Local Institution - Unk078
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Local Institution - Unk067
🇫🇷Marseille, France
Local Institution - 017-200
🇫🇷Montpellier, France
Local Institution - 017-664
🇫🇷Paris cedex 05, France
Local Institution - Unk029
🇫🇷Paris, France
Hopital Tenon
🇫🇷Paris, France
Local Institution - 017-198
🇫🇷Saint Herblain, France
Hopital Foch
🇫🇷Suresnes, France
Hopital Larrey
🇫🇷Toulouse cedex 9, France
Gustave Roussy
🇫🇷Villejuif, France
Local Institution - 017-790
🇬🇪Batumi, Georgia
Local Institution - 017-789
🇬🇪Tbilisi, Georgia
Local Institution - 017-794
🇬🇪Tbilisi, Georgia
Local Institution - 017-791
🇬🇪Tbilisi, Georgia
University General Hospital of Heraklion (PAGNI)
🇬🇷Heraklion, Greece
University General Hospital of Larissa
🇬🇷Larissa, Greece
Metropolitan Hospital
🇬🇷Peiraias, Greece
Orszagos Koranyi Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Szekesfehervar, Hungary
Reformatus Pulmonologiai Centrum
🇭🇺Torokbalint, Hungary
Local Institution - 017-767 - B
🇮🇹Faenza, Ravenna, Italy
Local Institution - 017-767 - A
🇮🇹Lugo, Ravenna, Italy
Azienda Ospedaliera San Giuseppe Moscati - Avellino
🇮🇹Avellino, Italy
Local Institution - 017-274
🇮🇹Aviano, Italy
Ospedale Santo Spirito
🇮🇹Casale Monferrato, Italy
Azienda Ospedaliero - Universitaria Careggi
🇮🇹Firenze, Italy
Istituto Europeo di Oncologia
🇮🇹Milan, Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Local Institution - 017-297
🇮🇹Padova, Italy
Ospedale Santa Maria delle Croci di Ravenna
🇮🇹Ravenna, Italy
IRCCS Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Local Institution - 017-280
🇮🇹Roma, Italy
Local Institution - 017-076
🇲🇾Kota Bharu, Kelantan, Malaysia
Local Institution - 017-075
🇲🇾Kuantan, Pahang, Malaysia
Local Institution - 017-073
🇲🇾Kuala Lumpur, Malaysia
Local Institution - 017-072
🇲🇾Putrajaya, Malaysia
Local Institution - 017-381
🇵🇱Konin, Poland
Instytut MSF
🇵🇱Lodz, Poland
Med Polonia Sp. z o. o. - Obornicka
🇵🇱Poznan, Poland
Wojskowy Instytut Medyczny
🇵🇱Warsaw, Poland
Local Institution - 017-692
🇷🇸Belgrade, Serbia
Local Institution - 017-690
🇷🇸Belgrade, Serbia
Local Institution - 017-693
🇷🇸Beograd, Serbia
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruna, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Spain
Local Institution - Unk001
🇪🇸Malaga, Spain
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Local Institution - 017-395
🇨🇭Geneve, Switzerland
Local Institution - 017-132
🇹🇭Bang Phlat, Thailand
Local Institution - 017-136
🇹🇭Bangkok, Thailand
Local Institution - 017-135
🇹🇭Chom Thong, Thailand
Local Institution - 017-137
🇹🇭Khon Kaen, Thailand